Fetal development and neuronal/glial cell specificity of cAMP-dependent protein kinase subunit mRNAs in rat brain

All known actions of cAMP in the brain require cAMP-dependent protein kinase (cAMPdPK), which consists of regulatory (R) and catalytic (C) subunits (R2C2). Using homologous rat cDNAs for all known cAMPdPK subunit isoforms found in the brain (RI alpha, RI beta, RII alpha, RII beta, C alpha, C beta) we observe that, in the fetal rat brain from 12 days of gestation to birth, while alpha subunit (RI alpha, RII alpha, C alpha) mRNA levels are abundant, beta subunit (RI beta, RII beta, C beta) mRNA levels increase from undetectable or very low levels to abundant levels. Furthermore, while alpha subunit mRNA levels are abundant in both primary neuronal and primary glial cultures, beta subunit mRNA levels are very low (C beta) or undetectable (RI beta, RII beta) in primary glial cultures, but are abundant in primary neuronal cultures. Thus, prior to about 12 days of gestation, cAMP in the brain may act only via the alpha cAMPdPK subunits in neuronal and glial precursor cells. After 12 days of gestation, coincident with the onset of final cell division in neurons, beta cAMPdPK subunits may also mediate the effects of cAMP predominantly in neurons.